A5000898624- Chronic Lymphocytic Leukemia Research
- DNA Repair Mechanisms
- Cancer, Hypoxia, and Metabolism
- Multiple Sclerosis Research Studies
- Glioma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Polyomavirus and related diseases
- Lymphoma Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Mitochondrial Function and Pathology
- Lung Cancer Treatments and Mutations
- PARP inhibition in cancer therapy
- Fungal Plant Pathogen Control
- Brain Metastases and Treatment
- Lung Cancer Research Studies
- Viral-associated cancers and disorders
- Acute Myeloid Leukemia Research
- Multiple Myeloma Research and Treatments
- Cancer-related Molecular Pathways
- Head and Neck Cancer Studies
- Cancer Genomics and Diagnostics
- Bacteriophages and microbial interactions
- Cancer, Lipids, and Metabolism
- Neurological disorders and treatments
- Plant Virus Research Studies
Merck (Germany)
2013-2024
St. Michael's Hospital
2018
Northwestern University
2018
University of Toronto
2018
Vanderbilt University Medical Center
2018
Thomas Jefferson University
2018
University of Lausanne
2010
University of Bern
2010
University Hospital of Lausanne
2010
Purpose Invasion and migration are key processes of glioblastoma tightly linked to tumor recurrence. Integrin inhibition using cilengitide has shown synergy with chemotherapy radiotherapy in vitro promising activity recurrent glioblastoma. This multicenter, phase I/IIa study investigated the efficacy safety combination standard chemoradiotherapy newly diagnosed Patients Methods (age ≥ 18 ≤ 70 years) were treated (500 mg) administered twice weekly intravenously addition concomitant adjuvant...
Survival outcomes for patients with glioblastoma remain poor, particularly unmethylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens selective integrin inhibitor cilengitide combined standard chemoradiotherapy in newly diagnosed an MGMT Overall, 265 were randomized (1:1:1) to (2000 mg 2×/wk; n = 88), intensive 5×/wk during wk 1−6, thereafter or a control arm...
Abstract The objective of this study is to conduct a dose‐finding sarizotan in Parkinson's disease (PD) patients with dyskinesia identify safe dose and sensitive rating measure. Sarizotan novel compound full 5‐HT 1A agonist properties additional high affinity for D 3 4 receptors. An open label documented improvements PD levodopa‐induced dyskinesia. There no precedent designs or outcome measures pivotal trials antidyskinesia therapies. approach used here was multicenter, randomized,...
Immune reconstitution therapies (IRT) for patients with multiple sclerosis are used short, intermittent treatment periods to induce immune resetting and allow subsequent treatment-free periods. Cladribine tablets postulated be an IRT that causes selective transient reductions in CD19+ B cells T cells, followed by of adaptive function.To characterize long-term lymphocyte count changes pooled data from the 2-year CLARITY Extension studies, PREMIERE registry (Long-term cohort).Data randomized...
Tuvusertib (M1774) is a potent, selective, orally administered ataxia telangiectasia and Rad3-related (ATR) protein kinase inhibitor. This first-in-human study (NCT04170153) evaluated safety, tolerability, maximum tolerated dose (MTD), recommended for expansion (RDE), pharmacokinetics (PK), pharmacodynamics (PD), preliminary efficacy of tuvusertib monotherapy.
Abstract Clinical features that are prognostic indicators of placebo response among dyskinetic Parkinson's disease patients were determined. Placebo‐associated improvements occur in Parkinsonism, but responses dyskinesia have not been studied. Placebo data from two multicenter studies with identical design comparing sarizotan to for treating accessed. Sarizotan (2 mg/day) failed improve compared placebo, both treatments improved baseline. Stepwise regression identified baseline...
Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvβ5 integrin. Cilengitide selectively inhibits αvβ3 integrins is investigated as a treatment strategy.
// Michael Weller 1 , Louis Burt Nabors 2 Thierry Gorlia 3 Henning Leske 4 Elisabeth Rushing Pierre Bady 5, 6, 7 Christine Hicking 8 James Perry 9 Yong-Kil Hong 10 Patrick Roth Wolfgang Wick 11, 12 Simon L. Goodman Monika E. Hegi Martin Picard Holger Moch 13 Josef Straub Roger Stupp 14 Department of Neurology, University Hospital Zurich and Zurich, Switzerland Alabama at Birmingham, AL, USA EORTC Data Centre, Brussels, Belgium Institute Neuropathology, 5 Education Research, Lausanne, 6 SIB...
Background: Neuroimaging studies have used magnetic resonance imaging-derived methods to assess brain volume loss in multiple sclerosis (MS) as a reliable measure of diffuse tissue damage. Methods: In the CLARITY study ( ClinicalTrials.gov NCT00213135), effect 2 years’ treatment with cladribine tablets on annualized percentage change (PBVC/y) was evaluated patients relapsing MS (RMS). Results: Compared placebo (–0.70% ± 0.79), PBVC/y reduced treated 3.5 mg/kg (–0.56% 0.68, p = 0.010) and...
Background: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting sclerosis. Objective: Describe two clinically relevant definitions for high disease activity (HDA) at baseline of study (utility verified receiving assess treatment effects 3.5 mg/kg compared overall population. Methods: Outcomes randomised to or placebo were...
<h3>Objective</h3> To evaluate the safety and efficacy of cladribine tablets in patients still experiencing active relapsing MS despite interferon (IFN)-β treatment. <h3>Methods</h3> A 96-week phase II study, randomizing treated with IFN-β to 3.5 mg/kg/IFN-β or placebo/IFN-β. Patients were receive placebo/IFN-β a 2:1 ratio (n = 172) exploratory outcomes being assessed. <h3>Results</h3> Adverse events (AEs) serious AEs similar across treatment groups, except lymphopenia. Fifty 124 (40.3%)...
LBA2009 Background: Cilengitide (CIL) is a selective αvβ3 and αvβ5 integrin inhibitor. In phase II study in patients with newly diagnosed glioblastoma, CIL added to standard temozolomide (TMZ) radiotherapy (RT) was well tolerated appeared confer improved survival glioblastoma methylated MGMT gene promoter (Stupp et al. J Clin Oncol. 2010;28:2712-8). Methods: This multicenter, randomized, controlled, open-label, III randomized (1:1) (≥ 18 years) diagnosed, histologically proven supratentorial...
9507 Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with poor prognosis. Studies of second-line chemotherapy for metastatic MCC (mMCC) have reported median progression-free survival (PFS) up to 3 months and no benefit overall (OS). Avelumab, human anti–PD-L1 monoclonal antibody, approved in several countries the treatment mMCC. Here, we report updated efficacy safety data from part A pivotal, single-arm, phase 2, JAVELIN 200 trial avelumab patients (pts) mMCC ≥2 y...
2010 Background: Prognosis of patients with recurrent glioblastoma multiforme (GBM) is poor. Cilengitide an investigational selective αvβ3/5 integrin inhibitor multiple anti-tumor effects. In a randomized phase IIa trial cilengitide in GBM, median overall survival (OS) was 9.9 months (2,000 mg arm) vs. 6.5 (500 [Reardon et al, JCO 2008]. Long-term follow up data are reported here. Methods: A randomized, multicenter, open-label examined effects 2 monotherapy regimens: 500 (n = 41) and 2,000...
3018 Background: Ataxia telangiectasia and Rad3-related (ATR) protein kinase poly-ADP ribose polymerases (PARPs) are crucial components in the DNA damage response (DDR). Combining tuvusertib niraparib may synergistically enhance synthetic lethality increase apoptosis. Part B1 of DDRiver Solid Tumors 301 study (NCT04170153) assessed this combination. Methods: open-label multicenter dose-escalation phase Ib trial enrolled unselected patients with metastatic or locally advanced unresectable...
Objective: To assess the efficacy of cladribine tablets (3.5mg/kg) as an add-on to IFN-β in patients with active relapsing MS Background: Cladribine given annually for 2 years short-duration courses RRMS significantly improved clinical and MRI outcomes (CLARITY). In CLARITY Extension, benefits 2-years treatment (3.5mg/kg bodyweight) were maintained study 4 or more without further treatment. ONWARD evaluated safety/tolerability therapy. Efficacy is reported here. Methods: was a 2-year,...
Abstract M4076 is a potent and selective oral inhibitor of ataxia-telangiectasia mutated (ATM), key kinase the DNA damage response (DDR) involved in double-strand break repair. Preclinically, when combined with damage-inducing therapy or other DDR inhibitors caused unrestricted cell cycle progression accumulation, resulting tumor death. Part 1A this ongoing open-label study (NCT04882917) evaluated safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), maximum tolerated dose...
Cladribine Tablets (MAVENCLAD®) selectively reduce absolute lymphocyte counts (ALCs) in patients with multiple sclerosis. The recommended cumulative dose of is 3.5 mg/kg over 4–5 days months 1 and 2 treatment years 2, followed by prolonged efficacy no additional treatment. After the cladribine-induced reduction, ALCs recover to normal within each year most patients. Those slow ALC recovery can develop Grade 3–4 lymphopenia, especially those ≥ lymphopenia at start 2. Guidelines allowing...
Abstract Background: Ataxia telangiectasia and Rad3-related (ATR) protein kinase plays a critical role in the DNA damage response. M1774, potent, selective, orally administered ATR inhibitor with antitumor activity preclinical models, was evaluated as monotherapy Part A1 of first-in-human open-label, single-arm study (NCT04170153). M1774 well-tolerated pharmacodynamic analyses showed that maximum target engagement reached from dose 130 mg QD. The totality evidence, including quantitative...